1. Field of the Invention
The present invention relates to a biodegradable thermo-sensitive polymer for medical use and, more particularly, to a biodegradable thermo-sensitive polymer for a drug delivery system or embolic agents.
2. Description of Related Art
Several biodegradable polymers have been developed in the past decades for acting as drug release systems for treating chronic diseases in humans. In 1988, Churchill et al. suggested a dispersed polymer for improving the aqueous solubility and the stability of the biodegradable polymers for drug delivery purposes (see U.S. Pat. No. 4,745,160). However, owing to the requirement of dispersity, the application of these biodegradable polymers is limited. For improving the processibility and flexibility of biodegradable copolymers, Song et al. disclosed a multi-block biodegradable copolymer in U.S. Pat. No. 5,514,380. However, since organic solvents are used in the complex manufacturing processes, the application of these biodegradable copolymers continue to be investigated. In 1997, thermosensitive biodegradable tri-block copolymers were disclosed by Cha et al. (see U.S. Pat. No. 5,702,717). These tri-block copolymers are suitable for drug delivery purposes because of their improved biodegradability and high thermo-sensitivity. However, since toxic monomers (e.g. diisocyanates) are used for manufacturing these thermo-sensitive biodegradable tri-block copolymers, the application of these tri-block copolymers in a human body is still limited. Moreover, these thermo-sensitive copolymers illustrated above cannot prevent the bursting out of drugs from the polymeric drug delivery system in a short initial period of drug administration time (burst effect). Therefore, these thermo-sensitive polymers for drug delivery purposes still cannot be widely used.
On the other hand, in some cases, biodegradable polymers functioning as embolic agents for blocking the supply of nutrients to the disordered tissues or cancer cells through arteries are also in demand. However, suitable biodegradable polymers for functioning as embolic agents without toxicity are rare. In addition, the application of the polymeric embolic agents is also limited by the methods for implanting. So far, thermo-sensitive polymers have been suggested to be suitable candidates for embolic agents because of simple implantation (e.g. injection) methods and easy formation of gels. Nevertheless, the toxicity and the biodegradability have become new issues to be solved for these thermo-sensitive polymers. Moreover, thermo-sensitive polymers have also been proposed to be a carrier for biological molecules. For example, copolymers of N-isopropylacrylamide and acrylic monomers were suggested to be used as implantable biohybrid pancreas in which pancreatic islets were encapsulated (see U.S. Pat. No. 5,262,055). However, since poly(NIPAAm) is not a biodegradable polymer, its application in a human body is seriously limited.
In order to achieve the application of thermo-sensitive polymers for functioning as drug delivery systems and embolic agents, it is desirable to provide an improved method to mitigate the aforementioned problems.